tbuckley/cabot-search huggingface dataset:
Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles
Authors: Ruyi Wang, Shijie Cao, Mohamed Elfatih H. Bashir, Lauren A. Hesser, Yanlin Su, Sung Min Choi Hong, Andrew Thompson, Elliot Culleen, Matthew Sabados, Nicholas P. Dylla, Evelyn Campbell, Riyue Bao, Eric B. Nonnecke, Charles L. Bevins, D. Scott Wilson, Jeffrey A. Hubbell, Cathryn R. Nagler
Journal: Nature Biomedical Engineering (2022)

The microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases.
Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons — 43 U.S. Jurisdictions, July 31–October 1, 2022
Authors: Amanda B. Payne, Logan C. Ray, Matthew M. Cole, Michelle Canning, Kennedy Houck, Hazel J. Shah, Jennifer L. Farrar, Nathaniel M. Lewis, Amy Fothergill, Elizabeth B. White, Leora R. Feldstein, Lauren E. Roper, Florence Lee, Jennifer L. Kriss, Emily Sims, Ian H. Spicknall, Yoshinori Nakazawa, Adi V. Gundlapalli, Tom Shimabukuro, Adam L. Cohen, Margaret A. Honein, Jonathan Mermin, Daniel C. Payne
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply† (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States.§ To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men¶ aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection†† (5).
Gut microbiota-mediated nucleotide synthesis attenuates the response to neoadjuvant chemoradiotherapy in rectal cancer
Authors: Huajing Teng, Yan Wang, Xin Sui, Jiawen Fan, Shuai Li, Xiao Lei, Chen Shi, Wei Sun, Maxiaowei Song, Hongzhi Wang, Dezuo Dong, Jianhao Geng, Yangzi Zhang, Xianggao Zhu, Yong Cai, Yongheng Li, Bo Li, Qingjie Min, Weihu Wang, Qimin Zhan
Journal: Cancer Cell (2022)

Preoperative neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for locally advanced rectal cancer (LARC) patients, yet little is known about the mediators underlying the heterogeneous patient response. In this longitudinal study, we performed 16S rRNA sequencing on 353 fecal specimens and find reduced microbial diversity after nCRT. Multi-omics data integration reveals that Bacteroides vulgatus-mediated nucleotide biosynthesis associates with nCRT resistance in LARC patients, and nonresponsive tumors are characterized by the upregulation of genes related to DNA repair and nucleoside transport. Nucleosides supplementation or B. vulgatus gavage protects cancer cells from the 5-fluorouracil or irradiation treatment. An analysis of 2,205 serum samples from 735 patients suggests that uric acid is a potential prognosis marker for LARC patients receiving nCRT. Our data unravel the role of intestinal microbiota-mediated nucleotide biosynthesis in the response of rectal tumors to nCRT, and highlight the importance of deciphering the cross-talk between cancer cells and gut microorganisms during cancer therapies.
Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial
Authors: Aikaterini Panopoulou, David A. Cairns, Amy Holroyd, Isabel Nichols, Nikita Cray, Charlotte Pawlyn, Gordon Cook, Mark Drayson, Kevin Boyd, Faith E. Davies, Matthew Jenner, Gareth J. Morgan, Roger Owen, Richard Houlston, Graham Jackson, Martin F. Kaiser
Journal: Blood (2022)

Prediction of individual patient benefit from lenalidomide (Len) maintenance after autologous stem cell transplant (ASCT) remains challenging. Here, we investigated extended molecular profiling for outcome prediction in patients in the National Cancer Research Institute Myeloma XI (MyXI) trial. Patients in the MyXI trial randomized to Len maintenance or observation after ASCT were genetically profiled for t(4;14), t(14;16), t(14;20), del(1p), gain(1q), and del(17p) and co-occurrence of risk markers was computed. Progression-free survival (PFS), subsequent progression (PFS2), and overall survival (OS) were calculated from maintenance randomization, and groups were compared using Cox proportional hazards regression. Of 556 patients, 17% with double-hit multiple myeloma (MM) (≥2 risk markers), 32% with single-hit (1 risk marker), and 51% without risk markers were analyzed. Single-hit MM derived the highest PFS benefit from Len maintenance, specifically, isolated del(1p), del(17p), and t(4;14), with ∼40-fold, 10-fold, and sevenfold reduced risk of progression or death (PFS), respectively, compared with observation. This benefit translated into improved PFS2 and OS for this group of patients compared with observation; median PFS was 10.9 vs 57.3 months for observation vs Len maintenance. Patients with isolated gain(1q) derived no benefit, and double-hit MM limited benefit (regardless or risk lesions involved) from Len maintenance. Extended genetic profiling identifies patients deriving exceptional benefit from Len maintenance and should be considered for newly diagnosed patients to support management discussions along their treatment pathway. This trial was registered at www.isrctn.com/ISRCTN49407852 as # ISRCTN49407852.
SOX2‐positive retinal stem cells are identified in adult human pars plicata by single‐cell transcriptomic analyses
Authors: Xiaotang Wang, Wei Fan, Zongren Xu, Qi Zhang, Na Li, Ruonan Li, Guoqing Wang, Siyuan He, Wanqian Li, Dan Liao, Zhi Zhang, Nan Shu, Jiaxing Huang, Chenyang Zhao, Shengping Hou
Journal: MedComm (2022)

Stem cell therapy is a promising strategy to rescue visual impairment caused by retinal degeneration. Previous studies have proposed controversial theories about whether in situ retinal stem cells (RSCs) are present in adult human eye tissue. Single-cell RNA sequencing (scRNA-seq) has emerged as one of the most powerful tools to reveal the heterogeneity of tissue cells. By using scRNA-seq, we explored the cell heterogeneity of different subregions of adult human eyes, including pars plicata, pars plana, retinal pigment epithelium (RPE), iris, and neural retina (NR). We identified one subpopulation expressing SRY-box transcription factor 2 (SOX2) as RSCs, which were present in the pars plicata of the adult human eye. Further analysis showed the identified subpopulation of RSCs expressed specific markers aquaporin 1 (AQP1) and tetraspanin 12 (TSPAN12). We, therefore, isolated this subpopulation using these two markers by flow sorting and found that the isolated RSCs could proliferate and differentiate into some retinal cell types, including photoreceptors, neurons, RPE cells, microglia, astrocytes, horizontal cells, bipolar cells, and ganglion cells; whereas, AQP1
Two isoleucyl tRNAs that decode synonymous codons divergently regulate breast cancer metastatic growth by controlling translation of proliferation-regulating genes
Authors: Lisa B. Earnest-Noble, Dennis Hsu, Siyu Chen, Hosseinali Asgharian, Mandayam Nandan, Maria C. Passarelli, Hani Goodarzi, Sohail F. Tavazoie
Journal: Nature Cancer (2022)
Alterations in the cutaneous microbiome of patients with psoriasis and psoriatic arthritis reveal similarities between non-lesional and lesional skin
Authors: Alba Boix-Amorós, Michelle H Badri, Julia Manasson, Rebecca B Blank, Rebecca H Haberman, Andrea L Neimann, Parvathy V Girija, Anthony Jimenez Hernandez, Adriana Heguy, Sergei B Koralov, Richard Bonneau, Jose C Clemente, Jose U Scher
Journal: Annals of the Rheumatic Diseases (2022)

To investigate the cutaneous microbiome spanning the entire psoriatic disease spectrum, and to evaluate distinguishing features of psoriasis (PsO) and psoriatic arthritis (PsA).
Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review
Authors: Edris Choupani, Mohammad Mahmoudi Gomari, Saeed Zanganeh, Sherko Nasseri, Kaveh Haji-allahverdipoor, Neda Rostami, Yaeren Hernandez, Safa Najafi, Neda Saraygord-Afshari, Arshad Hosseini
Journal: Pharmacological Reviews (2022)

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC; therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cell's nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPR/Cas9 and nanotechnology as state-of-the-art approaches against AR to promote the efficiency of targeted therapy in TNBC. <h3>Significance Statement</h3> The lack of effective treatment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly improving the survival rate of breast cancer patients.
Targeting Persistent Changes in Neuroimmune and Epigenetic Signaling in Adolescent Drinking to Treat Alcohol Use Disorder in Adulthood
Authors: Fulton T. Crews, Leon G. Coleman, Victoria A. Macht, Ryan P. Vetreno
Journal: Pharmacological Reviews (2022)

Studies universally find early age of drinking onset is linked to lifelong risks of alcohol problems and alcohol use disorder (AUD). Assessment of the lasting effect of drinking during adolescent development in humans is confounded by the diversity of environmental and genetic factors that affect adolescent development, including emerging personality disorders and progressive increases in drinking trajectories into adulthood. Preclinical studies using an adolescent intermittent ethanol (AIE) exposure rat model of underage binge drinking avoid the human confounds and support lifelong changes that increase risks. AIE increases adult alcohol drinking, risky decision-making, reward-seeking, and anxiety as well as reductions in executive function that all increase risks for the development of an AUD. AIE causes persistent increases in brain neuroimmune signaling high-mobility group box 1 (HMGB1), Toll-like receptor, receptor for advanced glycation end products, and innate immune genes that are also found to be increased in human AUD brain. HMGB1 is released from cells by ethanol, both free and within extracellular vesicles, that act on neurons and glia, shifting transcription and cellular phenotype. AIE-induced decreases in adult hippocampal neurogenesis and loss of basal forebrain cholinergic neurons are reviewed as examples of persistent AIE-induced pathology. Both are prevented and reversed by anti-inflammatory and epigenetic drugs. Findings suggest AIE-increased HMGB1 signaling induces the RE-1 silencing transcript blunting cholinergic gene expression, shifting neuronal phenotype. Inhibition of HMGB1 neuroimmune signaling, histone methylation enzymes, and galantamine, the cholinesterase inhibitor, both prevent and reverse AIE pathology. These findings provide new targets that may reverse AUD neuropathology as well as other brain diseases linked to neuroimmune signaling. <h3>Significance Statement</h3> Adolescent underage binge drinking studies find that earlier adolescent drinking is associated with lifelong alcohol problems including high levels of lifetime alcohol use disorder (AUD). Preclinical studies find the underage binge drinking adolescent intermittent ethanol (AIE) model causes lasting changes in adults that increase risks of developing adult alcohol problems. Loss of hippocampal neurogenesis and loss of basal forebrain cholinergic neurons provide examples of how AIE-induced epigenetic and neuroimmune signaling provide novel therapeutic targets for adult AUD.
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial
Authors: Christopher C Butler, F D Richard Hobbs, Oghenekome A Gbinigie, Najib M Rahman, Gail Hayward, Duncan B Richards, Jienchi Dorward, David M Lowe, Joseph F Standing, Judith Breuer, Saye Khoo, Stavros Petrou, Kerenza Hood, Jonathan S Nguyen-Van-Tam, Mahendra G Patel, Benjamin R Saville, Joe Marion, Emma Ogburn, Julie Allen, Heather Rutter, Nick Francis, Nicholas P B Thomas, Philip Evans, Melissa Dobson, Tracie-Ann Madden, Jane Holmes, Victoria Harris, May Ee Png, Mark Lown, Oliver van Hecke, Michelle A Detry, Christina T Saunders, Mark Fitzgerald, Nicholas S Berry, Lazaro Mwandigha, Ushma Galal, Sam Mort, Bhautesh D Jani, Nigel D Hart, Haroon Ahmed, Daniel Butler, Micheal McKenna, Jem Chalk, Layla Lavallee, Elizabeth Hadley, Lucy Cureton, Magdalena Benysek, Monique Andersson, Maria Coates, Sarah Barrett, Clare Bateman, Jennifer C Davies, Ivy Raymundo-Wood, Andrew Ustianowski, Andrew Carson-Stevens, Ly-Mee Yu, Paul Little, Akosua A Agyeman, Tanveer Ahmed, Damien Allcock, Adrian Beltran-Martinez, Oluseye E Benedict, Nigel Bird, Laura Brennan, Julianne Brown, Gerard Burns, Mike Butler, Zelda Cheng, Ruth Danson, Nigel de Kare-Silver, Devesh Dhasmana, Jon Dickson, Serge Engamba, Stacey Fisher, Robin Fox, Eve Frost, Richard Gaunt, Sarit Ghosh, Ishtiaq Gilkar, Anna Goodman, Steve Granier, Aleksandra Howell, Iqbal Hussain, Simon Hutchinson, Marie Imlach, Greg Irving, Nicholas Jacobsen, James Kennard, Umar Khan, Kyle Knox, Christopher Krasucki, Tom Law, Rem Lee, Nicola Lester, David Lewis, James Lunn, Claire I. Mackintosh, Mehul Mathukia, Patrick Moore, Seb Morton, Daniel Murphy, Rhiannon Nally, Chinonso Ndukauba, Olufunto Ogundapo, Henry Okeke, Amit Patel, Kavil Patel, Ruth Penfold, Satveer Poonian, Olajide Popoola, Alexander Pora, Vibhore Prasad, Rishabh Prasad, Omair Razzaq, Scot Richardson, Simon Royal, Afsana Safa, Satash Sehdev, Tamsin Sevenoaks, Divya Shah, Aadil Sheikh, Vanessa Short, Baljinder S Sidhu, Ivor Singh, Yusuf Soni, Chris Thalasselis, Pete Wilson, David Wingfield, Michael Wong, Maximillian N J Woodall, Nick Wooding, Sharon Woods, Joanna Yong, Francis Yongblah, Azhar Zafar
Journal: The Lancet (2022)
ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific, brain-penetrating fusion protein
Authors: Gillian Bonvicini, Stina Syvänen, Ken G. Andersson, Merja Haaparanta-Solin, Francisco López-Picón, Dag Sehlin
Journal: Translational Neurodegeneration (2022)

Abstract Background Hijacking the transferrin receptor (TfR) is an effective strategy to transport amyloid-beta (Aβ) immuno-positron emission tomography (immunoPET) ligands across the blood–brain barrier (BBB). Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβ pathology in mouse models of Alzheimer’s disease (AD). This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET radioligands. Methods Two affinity variants of the rat TfR antibody, OX26, were chemically conjugated to a F(ab′) 2 fragment of the anti-Aβ antibody, bapineuzumab (Bapi), to generate two bispecific fusion proteins: OX26 5 -F(ab′) 2 -Bapi and OX26 76 -F(ab′) 2 -Bapi. Pharmacokinetic analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type (WT) rats. [ 124 I]I-OX26 5 -F(ab′) 2 -Bapi was administered to TgF344-AD and WT rats for in vivo PET imaging. Ex vivo distribution of injected [ 124 I]I-OX26 5 -F(ab′) 2 -Bapi and Aβ pathology were assessed. Results More [ 125 I]I-OX26 5 -F(ab′) 2 -Bapi was taken up into the brain 4 h post-administration than [ 124 I]I-OX26 76 -F(ab′) 2 -Bapi. [ 124 I]I-OX26 5 -F(ab′) 2 -Bapi PET visualized Aβ pathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβ pathology. The PET signals significantly correlated with Aβ levels in AD animals. Conclusion Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB, such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently. Furthermore, bispecific immunoPET imaging of brain Aβ pathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats, suggesting that this immunoPET strategy has the potential to be translated to higher species.
Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: uncovering novel targets to combat astrocyte-mediated toxicity
Authors: Winanto Ng, Shi-Yan Ng
Journal: Translational Neurodegeneration (2022)

Amyotrophic lateral sclerosis (ALS) is an adult-onset paralytic disease characterized by progressive degeneration of upper and lower motor neurons in the motor cortex, brainstem and spinal cord. Motor neuron degeneration is typically caused by a combination of intrinsic neuronal (cell autonomous) defects as well as extrinsic (non-cell autonomous) factors such as astrocyte-mediated toxicity. Astrocytes are highly plastic cells that react to their microenvironment to mediate relevant responses. In neurodegeneration, astrocytes often turn reactive and in turn secrete a slew of factors to exert pro-inflammatory and neurotoxic effects. Various efforts have been carried out to characterize the diseased astrocyte secretome over the years, revealing that pro-inflammatory chemokines, cytokines and microRNAs are the main players in mediating neuronal death. As metabolomic technologies mature, these studies begin to shed light on neurotoxic metabolites such as secreted lipids. In this focused review, we will discuss changes in the astrocyte secretome during ALS. In particular, we will discuss the components of the reactive astrocyte secretome that contribute to neuronal death in ALS.
Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression
Authors: Fei Pei, Ren-Qi Yao, Chao Ren, Soheyl Bahrami, Timothy R. Billiar, Irshad H. Chaudry, De-Chang Chen, Xu-Lin Chen, Na Cui, Xiang-Ming Fang, Yan Kang, Wei-Qin Li, Wen-Xiong Li, Hua-Ping Liang, Hong-Yuan Lin, Ke-Xuan Liu, Ben Lu, Zhong-Qiu Lu, Marc Maegele, Tian-Qing Peng, You Shang, Lei Su, Bing-Wei Sun, Chang-Song Wang, Jian Wang, Jiang-Huai Wang, Ping Wang, Jian-Feng Xie, Li-Xin Xie, Li-Na Zhang, Basilia Zingarelli, Xiang-Dong Guan, Jian-Feng Wu, Yong-Ming Yao
Journal: Military Medical Research (2022)

Abstract Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.